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Center for Computational Systems Medicine
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Fusion Gene and Fusion Protein Summary

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Fusion Amino Acid Sequences (multiple BPs and multiple gene isoforms)

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Fusion Protein Breakpoint Sequences - (for the Screening of the FusionNeoAntigens)

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Potential FusionNeoAntigens in HLA I - (netMHCpan v4.1 + deepHLApan v1.1)

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Potential FusionNeoAntigens in HLA II - (netMHCIIpan v4.1)

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Fusion Breakpoint 14 AA Peptide Structure - (RoseTTAFold)

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D - (Glide)

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Vaccine Design for the FusionNeoAntigens (RNA/protein sequences)

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Potential target of CAR-T therapy development

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Information on the samples that have these potential fusion neoantigens

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Fusion Protein Targeting Drugs - (Manual Curation)

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Fusion Protein Related diseases - (Manual Curation)

Fusion Protein:AKAP13-NTRK3

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: AKAP13-NTRK3
FusionPDB ID: 3311
FusionGDB2.0 ID: 3311
HgeneTgene
Gene symbol

AKAP13

NTRK3

Gene ID

11214

4916

Gene nameA-kinase anchoring protein 13neurotrophic receptor tyrosine kinase 3
SynonymsAKAP-13|AKAP-Lbc|ARHGEF13|BRX|HA-3|Ht31|LBC|PRKA13|PROTO-LB|PROTO-LBC|c-lbc|p47GP145-TrkC|TRKC|gp145(trkC)
Cytomap

15q25.3

15q25.3

Type of geneprotein-codingprotein-coding
DescriptionA-kinase anchor protein 13A kinase (PRKA) anchor protein 13LBC oncogenebreast cancer nuclear receptor-binding auxiliary proteinguanine nucleotide exchange factor Lbchuman thyroid-anchoring protein 31lymphoid blast crisis oncogenenon-oncogenic Rho GNT-3 growth factor receptorETS related protein-neurotrophic receptor tyrosine kinase fusion proteinETV6-NTRK3 fusionneurotrophic tyrosine kinase, receptor, type 3tyrosine kinase receptor C
Modification date2020031320200313
UniProtAcc

Q12802

Main function of 5'-partner protein: FUNCTION: Scaffold protein that plays an important role in assembling signaling complexes downstream of several types of G protein-coupled receptors. Activates RHOA in response to signaling via G protein-coupled receptors via its function as Rho guanine nucleotide exchange factor (PubMed:11546812, PubMed:15229649, PubMed:23090968, PubMed:25186459, PubMed:24993829). May also activate other Rho family members (PubMed:11546812). Part of a kinase signaling complex that links ADRA1A and ADRA1B adrenergic receptor signaling to the activation of downstream p38 MAP kinases, such as MAPK11 and MAPK14 (PubMed:17537920, PubMed:23716597, PubMed:21224381). Part of a signaling complex that links ADRA1B signaling to the activation of RHOA and IKBKB/IKKB, leading to increased NF-kappa-B transcriptional activity (PubMed:23090968). Part of a RHOA-dependent signaling cascade that mediates responses to lysophosphatidic acid (LPA), a signaling molecule that activates G-protein coupled receptors and potentiates transcriptional activation of the glucocorticoid receptor NR3C1 (PubMed:16469733). Part of a signaling cascade that stimulates MEF2C-dependent gene expression in response to lysophosphatidic acid (LPA) (By similarity). Part of a signaling pathway that activates MAPK11 and/or MAPK14 and leads to increased transcription activation of the estrogen receptors ESR1 and ESR2 (PubMed:9627117, PubMed:11579095). Part of a signaling cascade that links cAMP and EGFR signaling to BRAF signaling and to PKA-mediated phosphorylation of KSR1, leading to the activation of downstream MAP kinases, such as MAPK1 or MAPK3 (PubMed:21102438). Functions as scaffold protein that anchors cAMP-dependent protein kinase (PKA) and PRKD1. This promotes activation of PRKD1, leading to increased phosphorylation of HDAC5 and ultimately cardiomyocyte hypertrophy (By similarity). Has no guanine nucleotide exchange activity on CDC42, Ras or Rac (PubMed:11546812). Required for normal embryonic heart development, and in particular for normal sarcomere formation in the developing cardiomyocytes (By similarity). Plays a role in cardiomyocyte growth and cardiac hypertrophy in response to activation of the beta-adrenergic receptor by phenylephrine or isoproterenol (PubMed:17537920, PubMed:23090968). Required for normal adaptive cardiac hypertrophy in response to pressure overload (PubMed:23716597). Plays a role in osteogenesis (By similarity). {ECO:0000250|UniProtKB:E9Q394, ECO:0000269|PubMed:11546812, ECO:0000269|PubMed:11579095, ECO:0000269|PubMed:17537920, ECO:0000269|PubMed:21224381, ECO:0000269|PubMed:23716597, ECO:0000269|PubMed:24993829, ECO:0000269|PubMed:25186459, ECO:0000269|PubMed:9627117, ECO:0000269|PubMed:9891067}.

Q16288

Main function of 5'-partner protein: FUNCTION: Receptor tyrosine kinase involved in nervous system and probably heart development. Upon binding of its ligand NTF3/neurotrophin-3, NTRK3 autophosphorylates and activates different signaling pathways, including the phosphatidylinositol 3-kinase/AKT and the MAPK pathways, that control cell survival and differentiation. {ECO:0000269|PubMed:25196463}.
Ensembl transtripts involved in fusion geneENST idsENST00000560579, ENST00000361243, 
ENST00000394510, ENST00000394518, 
ENST00000560302, 
ENST00000317501, 
ENST00000355254, ENST00000357724, 
ENST00000360948, ENST00000394480, 
ENST00000542733, ENST00000557856, 
ENST00000558676, ENST00000540489, 
ENST00000558306, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score37 X 24 X 13=1154415 X 19 X 11=3135
# samples 4115
** MAII scorelog2(41/11544*10)=-4.81537548498575
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(15/3135*10)=-4.38543103719352
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: AKAP13 [Title/Abstract] AND NTRK3 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: AKAP13 [Title/Abstract] AND NTRK3 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)AKAP13(86228104)-NTRK3(88576276), # samples:1
AKAP13(86213061)-NTRK3(88576276), # samples:1
Anticipated loss of major functional domain due to fusion event.AKAP13-NTRK3 seems lost the major protein functional domain in Hgene partner, which is a CGC by not retaining the major functional domain in the partially deleted in-frame ORF.
AKAP13-NTRK3 seems lost the major protein functional domain in Hgene partner, which is a CGC by not retaining the major functional domain in the partially deleted in-frame ORF.
AKAP13-NTRK3 seems lost the major protein functional domain in Hgene partner, which is a essential gene by not retaining the major functional domain in the partially deleted in-frame ORF.
AKAP13-NTRK3 seems lost the major protein functional domain in Hgene partner, which is a essential gene by not retaining the major functional domain in the partially deleted in-frame ORF.
AKAP13-NTRK3 seems lost the major protein functional domain in Tgene partner, which is a CGC due to the frame-shifted ORF.
AKAP13-NTRK3 seems lost the major protein functional domain in Tgene partner, which is a IUPHAR drug target due to the frame-shifted ORF.
AKAP13-NTRK3 seems lost the major protein functional domain in Tgene partner, which is a kinase due to the frame-shifted ORF.
AKAP13-NTRK3 seems lost the major protein functional domain in Tgene partner, which is a tumor suppressor due to the frame-shifted ORF.
* DoF score (Degree of Frequency) = # partners X # break points X # cancer types
** MAII score (Major Active Isofusion Index) = log2(# samples/DoF score*10)

check button Gene ontology of each fusion partner gene with evidence of Inferred from Direct Assay (IDA) from Entrez
PartnerGeneGO IDGO termPubMed ID
HgeneAKAP13

GO:0007186

G protein-coupled receptor signaling pathway

11546812

HgeneAKAP13

GO:0035025

positive regulation of Rho protein signal transduction

11546812

TgeneNTRK3

GO:0000187

activation of MAPK activity

23027130

TgeneNTRK3

GO:0001933

negative regulation of protein phosphorylation

23027130

TgeneNTRK3

GO:0007169

transmembrane receptor protein tyrosine kinase signaling pathway

23027130

TgeneNTRK3

GO:0008284

positive regulation of cell proliferation

23027130

TgeneNTRK3

GO:0010628

positive regulation of gene expression

23027130

TgeneNTRK3

GO:0030335

positive regulation of cell migration

23027130

TgeneNTRK3

GO:0032148

activation of protein kinase B activity

23027130

TgeneNTRK3

GO:0033138

positive regulation of peptidyl-serine phosphorylation

23027130

TgeneNTRK3

GO:0050927

positive regulation of positive chemotaxis

23027130

TgeneNTRK3

GO:0090630

activation of GTPase activity

23027130

TgeneNTRK3

GO:2000251

positive regulation of actin cytoskeleton reorganization

23027130



check button Four levels of functional features of fusion genes
Go to FGviewer search page for the most frequent breakpoint (https://ccsmweb.uth.edu/FGviewer/chr15:86228104/chr15:88576276)
- FGviewer provides the online visualization of the retention search of the protein functional features across DNA, RNA, protein, and pathological levels.
- How to search
1. Put your fusion gene symbol.
2. Press the tab key until there will be shown the breakpoint information filled.
4. Go down and press 'Search' tab twice.
4. Go down to have the hyperlink of the search result.
5. Click the hyperlink.
6. See the FGviewer result for your fusion gene.
FGviewer

check buttonRetention analysis results of each fusion partner protein across 39 protein features of UniProt such as six molecule processing features, 13 region features, four site features, six amino acid modification features, two natural variation features, five experimental info features, and 3 secondary structure features, are available here.

check buttonFusion gene breakpoints across AKAP13 (5'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.
all structure

check buttonFusion gene breakpoints across NTRK3 (3'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.
all structure


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Fusion Amino Acid Sequences


check buttonFusion information from ORFfinder translation from full-length transcript sequence from FusionPDB.
HenstTenstHgeneHchrHbpHstrandTgeneTchrTbpTstrandSeq length
(transcript)
BP loci
(transcript)
Predicted start
(transcript)
Predicted stop
(transcript)
Seq length
(amino acids)
ENST00000394518AKAP13chr1586213061-ENST00000394480NTRK3chr1588576276-821451969562772060
ENST00000394518AKAP13chr1586213061-ENST00000557856NTRK3chr1588576276-642251969562772060
ENST00000394518AKAP13chr1586213061-ENST00000357724NTRK3chr1588576276-646451969563192074
ENST00000394518AKAP13chr1586213061-ENST00000355254NTRK3chr1588576276-642251969562772060
ENST00000394518AKAP13chr1586213061-ENST00000360948NTRK3chr1588576276-646451969563192074
ENST00000394518AKAP13chr1586213061-ENST00000542733NTRK3chr1588576276-622151969559471950
ENST00000394518AKAP13chr1586213061-ENST00000558676NTRK3chr1588576276-612251969559411948
ENST00000394518AKAP13chr1586213061-ENST00000317501NTRK3chr1588576276-761751969556381847
ENST00000361243AKAP13chr1586213061-ENST00000394480NTRK3chr1588576276-821251948162752064
ENST00000361243AKAP13chr1586213061-ENST00000557856NTRK3chr1588576276-642051948162752064
ENST00000361243AKAP13chr1586213061-ENST00000357724NTRK3chr1588576276-646251948163172078
ENST00000361243AKAP13chr1586213061-ENST00000355254NTRK3chr1588576276-642051948162752064
ENST00000361243AKAP13chr1586213061-ENST00000360948NTRK3chr1588576276-646251948163172078
ENST00000361243AKAP13chr1586213061-ENST00000542733NTRK3chr1588576276-621951948159451954
ENST00000361243AKAP13chr1586213061-ENST00000558676NTRK3chr1588576276-612051948159391952
ENST00000361243AKAP13chr1586213061-ENST00000317501NTRK3chr1588576276-761551948156361851

check buttonDeepORF prediction of the coding potential based on the fusion transcript sequence of in-frame fusion genes. DeepORF is a coding potential classifier based on convolutional neural network by comparing the real Ribo-seq data. If the no-coding score < 0.5 and coding score > 0.5, then the in-frame fusion transcript is predicted as being likely translated.
HenstTenstHgeneHchrHbpHstrandTgeneTchrTbpTstrandNo-coding scoreCoding score
ENST00000394518ENST00000394480AKAP13chr1586213061-NTRK3chr1588576276-0.0013916850.9986083
ENST00000394518ENST00000557856AKAP13chr1586213061-NTRK3chr1588576276-0.0020592710.9979407
ENST00000394518ENST00000357724AKAP13chr1586213061-NTRK3chr1588576276-0.0018678160.99813217
ENST00000394518ENST00000355254AKAP13chr1586213061-NTRK3chr1588576276-0.0020592710.9979407
ENST00000394518ENST00000360948AKAP13chr1586213061-NTRK3chr1588576276-0.0018678160.99813217
ENST00000394518ENST00000542733AKAP13chr1586213061-NTRK3chr1588576276-0.0010230420.99897695
ENST00000394518ENST00000558676AKAP13chr1586213061-NTRK3chr1588576276-0.0012722110.99872774
ENST00000394518ENST00000317501AKAP13chr1586213061-NTRK3chr1588576276-0.0013517250.99864835
ENST00000361243ENST00000394480AKAP13chr1586213061-NTRK3chr1588576276-0.00121810.99878186
ENST00000361243ENST00000557856AKAP13chr1586213061-NTRK3chr1588576276-0.0017423470.9982577
ENST00000361243ENST00000357724AKAP13chr1586213061-NTRK3chr1588576276-0.0015917850.99840826
ENST00000361243ENST00000355254AKAP13chr1586213061-NTRK3chr1588576276-0.0017423470.9982577
ENST00000361243ENST00000360948AKAP13chr1586213061-NTRK3chr1588576276-0.0015917850.99840826
ENST00000361243ENST00000542733AKAP13chr1586213061-NTRK3chr1588576276-0.0019190570.99808097
ENST00000361243ENST00000558676AKAP13chr1586213061-NTRK3chr1588576276-0.0020443850.99795556
ENST00000361243ENST00000317501AKAP13chr1586213061-NTRK3chr1588576276-0.0009625640.9990375

check button Predicted full-length fusion amino acid sequences. For individual full-length fusion transcript sequence from FusionPDB, we ran ORFfinder and chose the longest ORF among all the predicted ones.

Get the fusion protein sequences from here.

Fusion protein sequence information is available in the fasta format.
>FusionGDB ID_FusionGDB isoform ID_FGname_Hgene_Hchr_Hbp_Henst_Tgene_Tchr_Tbp_Tenst_length(fusion AA) seq_BP

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Fusion Protein Breakpoint Sequences for AKAP13-NTRK3

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
AKAP13chr1586213061NTRK3chr158857627651941705ISLMTISHPGLDSPVAVISGEEDSAS
AKAP13chr1586213061NTRK3chr158857627651961701ISLMTISHPGLDSPVAVISGEEDSAS

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Potential FusionNeoAntigen Information of AKAP13-NTRK3 in HLA I

check button Multiple sequence alignments of the potential FusionNeoAntigens per fusion breakpoints. If the MSA is empty, then it means that there were predicted fusion neoantigens in this fusion breakpoint, but those predicted fusion neoantigens were not across the breakpoint, which is not fusion-specific.
AKAP13-NTRK3_86213061_88576276.msa

check button Potential FusionNeoAntigen Information
* We used NetMHCpan v4.1 (%rank<0.5) and deepHLApan v1.1 (immunogenic score>0.5)
Fusion geneHchrHbpTgeneTchrTbpHLA IFusionNeoAntigen peptideBinding scoreImmunogenic scoreNeoantigen start (at BP 13)Neoantigen end (at BP 13)
AKAP13-NTRK3chr1586213061chr15885762765194HLA-B39:01SHPGLDSPV0.99170.9599615
AKAP13-NTRK3chr1586213061chr15885762765194HLA-B56:01HPGLDSPVA0.98420.7362716
AKAP13-NTRK3chr1586213061chr15885762765194HLA-A02:67GLDSPVAVI0.97870.7304918
AKAP13-NTRK3chr1586213061chr15885762765194HLA-A02:30GLDSPVAVI0.97870.7304918
AKAP13-NTRK3chr1586213061chr15885762765194HLA-A02:24GLDSPVAVI0.97870.7304918
AKAP13-NTRK3chr1586213061chr15885762765194HLA-A02:60GLDSPVAVI0.97810.6919918
AKAP13-NTRK3chr1586213061chr15885762765194HLA-A02:16GLDSPVAVI0.97640.7166918
AKAP13-NTRK3chr1586213061chr15885762765194HLA-A02:11GLDSPVAVI0.97550.7408918
AKAP13-NTRK3chr1586213061chr15885762765194HLA-A02:27GLDSPVAVI0.97280.7858918
AKAP13-NTRK3chr1586213061chr15885762765194HLA-A02:38GLDSPVAVI0.9690.8459918
AKAP13-NTRK3chr1586213061chr15885762765194HLA-A02:13GLDSPVAVI0.9560.8404918
AKAP13-NTRK3chr1586213061chr15885762765194HLA-B55:01HPGLDSPVA0.95350.6278716
AKAP13-NTRK3chr1586213061chr15885762765194HLA-B35:03HPGLDSPVA0.93110.8576716
AKAP13-NTRK3chr1586213061chr15885762765194HLA-B15:10SHPGLDSPV0.90960.7012615
AKAP13-NTRK3chr1586213061chr15885762765194HLA-A02:19GLDSPVAVI0.85690.5411918
AKAP13-NTRK3chr1586213061chr15885762765194HLA-A02:35GLDSPVAVI0.84510.7359918
AKAP13-NTRK3chr1586213061chr15885762765194HLA-B35:02HPGLDSPVA0.83560.9716716
AKAP13-NTRK3chr1586213061chr15885762765194HLA-B35:04HPGLDSPVA0.83560.9716716
AKAP13-NTRK3chr1586213061chr15885762765194HLA-A02:29GLDSPVAVI0.80480.7331918
AKAP13-NTRK3chr1586213061chr15885762765194HLA-B39:06SHPGLDSPVA0.98670.9695616
AKAP13-NTRK3chr1586213061chr15885762765194HLA-B56:01HPGLDSPVAV0.98480.9196717
AKAP13-NTRK3chr1586213061chr15885762765194HLA-B35:03HPGLDSPVAV0.96590.839717
AKAP13-NTRK3chr1586213061chr15885762765194HLA-B51:02HPGLDSPVAV0.95280.8682717
AKAP13-NTRK3chr1586213061chr15885762765194HLA-B35:02HPGLDSPVAV0.94930.9696717
AKAP13-NTRK3chr1586213061chr15885762765194HLA-B35:04HPGLDSPVAV0.94930.9696717
AKAP13-NTRK3chr1586213061chr15885762765194HLA-B07:05HPGLDSPVAV0.94430.6769717
AKAP13-NTRK3chr1586213061chr15885762765194HLA-B55:01HPGLDSPVAV0.92390.8398717
AKAP13-NTRK3chr1586213061chr15885762765194HLA-B81:01HPGLDSPVAV0.72120.9226717
AKAP13-NTRK3chr1586213061chr15885762765194HLA-B82:01HPGLDSPVAV0.62520.8779717
AKAP13-NTRK3chr1586213061chr15885762765194HLA-B39:06SHPGLDSPVAV0.99940.9854617
AKAP13-NTRK3chr1586213061chr15885762765194HLA-B39:24SHPGLDSPVAV0.99930.9419617
AKAP13-NTRK3chr1586213061chr15885762765194HLA-B39:01SHPGLDSPVAV0.99910.9721617
AKAP13-NTRK3chr1586213061chr15885762765194HLA-B38:01SHPGLDSPVAV0.99890.9942617
AKAP13-NTRK3chr1586213061chr15885762765194HLA-B38:02SHPGLDSPVAV0.99890.9934617
AKAP13-NTRK3chr1586213061chr15885762765194HLA-B15:10SHPGLDSPVAV0.99420.7671617
AKAP13-NTRK3chr1586213061chr15885762765194HLA-B35:03HPGLDSPVAVI0.98440.8307718
AKAP13-NTRK3chr1586213061chr15885762765194HLA-B35:02HPGLDSPVAVI0.97310.9406718
AKAP13-NTRK3chr1586213061chr15885762765194HLA-B35:04HPGLDSPVAVI0.97310.9406718
AKAP13-NTRK3chr1586213061chr15885762765194HLA-C05:09GLDSPVAVI0.99990.9805918
AKAP13-NTRK3chr1586213061chr15885762765194HLA-C08:15GLDSPVAVI0.99960.9932918
AKAP13-NTRK3chr1586213061chr15885762765194HLA-B54:01HPGLDSPVA0.99150.9105716
AKAP13-NTRK3chr1586213061chr15885762765194HLA-B39:09SHPGLDSPV0.98850.924615
AKAP13-NTRK3chr1586213061chr15885762765194HLA-B39:05SHPGLDSPV0.98780.9521615
AKAP13-NTRK3chr1586213061chr15885762765194HLA-A02:07GLDSPVAVI0.97890.7163918
AKAP13-NTRK3chr1586213061chr15885762765194HLA-A02:01GLDSPVAVI0.97870.7304918
AKAP13-NTRK3chr1586213061chr15885762765194HLA-B56:04HPGLDSPVA0.95860.9117716
AKAP13-NTRK3chr1586213061chr15885762765194HLA-B35:12HPGLDSPVA0.83560.9716716
AKAP13-NTRK3chr1586213061chr15885762765194HLA-B54:01HPGLDSPVAV0.98860.9637717
AKAP13-NTRK3chr1586213061chr15885762765194HLA-B35:12HPGLDSPVAV0.94930.9696717
AKAP13-NTRK3chr1586213061chr15885762765194HLA-B56:04HPGLDSPVAV0.93520.9349717
AKAP13-NTRK3chr1586213061chr15885762765194HLA-B07:12HPGLDSPVAV0.9160.7437717
AKAP13-NTRK3chr1586213061chr15885762765194HLA-B78:01HPGLDSPVAV0.8110.9368717
AKAP13-NTRK3chr1586213061chr15885762765194HLA-B42:01HPGLDSPVAV0.71580.7656717
AKAP13-NTRK3chr1586213061chr15885762765194HLA-B51:08HPGLDSPVAV0.66550.8085717
AKAP13-NTRK3chr1586213061chr15885762765194HLA-B39:10HPGLDSPVAV0.60630.9693717
AKAP13-NTRK3chr1586213061chr15885762765194HLA-B39:09SHPGLDSPVAV0.99890.9751617
AKAP13-NTRK3chr1586213061chr15885762765194HLA-B39:05SHPGLDSPVAV0.99840.9681617
AKAP13-NTRK3chr1586213061chr15885762765194HLA-B35:12HPGLDSPVAVI0.97310.9406718
AKAP13-NTRK3chr1586213061chr15885762765194HLA-C05:01GLDSPVAVI0.99990.9805918
AKAP13-NTRK3chr1586213061chr15885762765194HLA-C04:03GLDSPVAVI0.99990.9663918
AKAP13-NTRK3chr1586213061chr15885762765194HLA-C08:02GLDSPVAVI0.99960.9932918
AKAP13-NTRK3chr1586213061chr15885762765194HLA-B55:02HPGLDSPVA0.96650.7978716
AKAP13-NTRK3chr1586213061chr15885762765194HLA-B56:02HPGLDSPVA0.95860.9117716
AKAP13-NTRK3chr1586213061chr15885762765194HLA-B15:09SHPGLDSPV0.92150.9016615
AKAP13-NTRK3chr1586213061chr15885762765194HLA-B35:09HPGLDSPVA0.83560.9716716
AKAP13-NTRK3chr1586213061chr15885762765194HLA-B56:05HPGLDSPVA0.79850.6839716
AKAP13-NTRK3chr1586213061chr15885762765194HLA-B67:01HPGLDSPVA0.58570.9652716
AKAP13-NTRK3chr1586213061chr15885762765194HLA-B39:11SHPGLDSPV0.55090.904615
AKAP13-NTRK3chr1586213061chr15885762765194HLA-B78:02HPGLDSPVA0.41670.8816716
AKAP13-NTRK3chr1586213061chr15885762765194HLA-B40:21GLDSPVAVI0.19190.7225918
AKAP13-NTRK3chr1586213061chr15885762765194HLA-B35:22HPGLDSPVAV0.98090.8616717
AKAP13-NTRK3chr1586213061chr15885762765194HLA-B55:02HPGLDSPVAV0.95330.9294717
AKAP13-NTRK3chr1586213061chr15885762765194HLA-B35:09HPGLDSPVAV0.94930.9696717
AKAP13-NTRK3chr1586213061chr15885762765194HLA-B56:02HPGLDSPVAV0.93520.9349717
AKAP13-NTRK3chr1586213061chr15885762765194HLA-B59:01HPGLDSPVAV0.91520.9083717
AKAP13-NTRK3chr1586213061chr15885762765194HLA-B55:04HPGLDSPVAV0.91210.8423717
AKAP13-NTRK3chr1586213061chr15885762765194HLA-B51:05HPGLDSPVAV0.88520.8524717
AKAP13-NTRK3chr1586213061chr15885762765194HLA-B51:29HPGLDSPVAV0.87240.7504717
AKAP13-NTRK3chr1586213061chr15885762765194HLA-B56:05HPGLDSPVAV0.8230.8816717
AKAP13-NTRK3chr1586213061chr15885762765194HLA-B78:02HPGLDSPVAV0.80380.9533717
AKAP13-NTRK3chr1586213061chr15885762765194HLA-B51:09HPGLDSPVAV0.80030.8358717
AKAP13-NTRK3chr1586213061chr15885762765194HLA-B07:26HPGLDSPVAV0.7940.7286717
AKAP13-NTRK3chr1586213061chr15885762765194HLA-B51:14HPGLDSPVAV0.7550.8235717
AKAP13-NTRK3chr1586213061chr15885762765194HLA-B51:13HPGLDSPVAV0.7470.8773717
AKAP13-NTRK3chr1586213061chr15885762765194HLA-B67:01HPGLDSPVAV0.68060.9767717
AKAP13-NTRK3chr1586213061chr15885762765194HLA-B82:02HPGLDSPVAV0.62520.8779717
AKAP13-NTRK3chr1586213061chr15885762765194HLA-B38:05SHPGLDSPVAV0.99890.9942617
AKAP13-NTRK3chr1586213061chr15885762765194HLA-B15:09SHPGLDSPVAV0.99260.9285617
AKAP13-NTRK3chr1586213061chr15885762765194HLA-B39:11SHPGLDSPVAV0.97810.9603617
AKAP13-NTRK3chr1586213061chr15885762765194HLA-B35:09HPGLDSPVAVI0.97310.9406718

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Potential FusionNeoAntigen Information of AKAP13-NTRK3 in HLA II

check button Multiple sequence alignments of the potential FusionNeoAntigens per fusion breakpoints. If the MSA is empty, then it means that there were predicted fusion neoantigens in this fusion breakpoint, but those predicted fusion neoantigens were not across the breakpoint, which is not fusion-specific.
AKAP13-NTRK3_86213061_88576276.msa

check button Potential FusionNeoAntigen Information
* We used NetMHCIIpan v4.1 (%rank<0.5).
Fusion geneHchrHbpTgeneTchrTbpHLA IIFusionNeoAntigen peptideNeoantigen start (at BP 13)Neoantigen end (at BP 13)
AKAP13-NTRK3chr1586213061chr15885762765194DRB1-0411DSPVAVISGEEDSAS1126
AKAP13-NTRK3chr1586213061chr15885762765194DRB1-0467DSPVAVISGEEDSAS1126
AKAP13-NTRK3chr1586213061chr15885762765194DRB1-0491DSPVAVISGEEDSAS1126

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Fusion breakpoint peptide structures of AKAP13-NTRK3

check button3D structures of the fusion breakpoint peptide of 14AA sequence that have potential fusion neoantigens
* The minimum length of the amino acid sequence in RoseTTAFold is 14AA. Here, we predicted the 14AA fusion protein breakpoint sequence not the fusion neoantigen peptide, which is shorter than 14 AA.
File nameBPseqHgeneTgeneHchrHbpTchrTbpAAlen
8627SHPGLDSPVAVISGAKAP13NTRK3chr1586213061chr15885762765194

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of AKAP13-NTRK3

check buttonVirtual screening between 25 HLAs (from PDB) and FusionNeoAntigens
* We used Glide to predict the interaction between HLAs and neoantigens.
HLA allelePDB IDFile nameBPseqDocking scoreGlide score
HLA-B14:023BVN8627SHPGLDSPVAVISG-7.15543-7.26883
HLA-B14:023BVN8627SHPGLDSPVAVISG-4.77435-5.80965
HLA-B52:013W398627SHPGLDSPVAVISG-6.80875-6.92215
HLA-B52:013W398627SHPGLDSPVAVISG-4.20386-5.23916
HLA-A11:014UQ28627SHPGLDSPVAVISG-7.5194-8.5547
HLA-A11:014UQ28627SHPGLDSPVAVISG-6.9601-7.0735
HLA-A24:025HGA8627SHPGLDSPVAVISG-7.52403-7.63743
HLA-A24:025HGA8627SHPGLDSPVAVISG-5.82433-6.85963
HLA-B27:056PYJ8627SHPGLDSPVAVISG-3.28285-4.31815
HLA-B44:053DX88627SHPGLDSPVAVISG-5.91172-6.94702
HLA-B44:053DX88627SHPGLDSPVAVISG-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of AKAP13-NTRK3

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-Is.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptide sequenceFusionNeoAntigen RNA sequence
AKAP13-NTRK3chr1586213061chr1588576276615SHPGLDSPVTCAGCCATCCTGGATTGGACAGTCCCG
AKAP13-NTRK3chr1586213061chr1588576276616SHPGLDSPVATCAGCCATCCTGGATTGGACAGTCCCGTGG
AKAP13-NTRK3chr1586213061chr1588576276617SHPGLDSPVAVTCAGCCATCCTGGATTGGACAGTCCCGTGGCTG
AKAP13-NTRK3chr1586213061chr1588576276716HPGLDSPVAGCCATCCTGGATTGGACAGTCCCGTGG
AKAP13-NTRK3chr1586213061chr1588576276717HPGLDSPVAVGCCATCCTGGATTGGACAGTCCCGTGGCTG
AKAP13-NTRK3chr1586213061chr1588576276718HPGLDSPVAVIGCCATCCTGGATTGGACAGTCCCGTGGCTGTCA
AKAP13-NTRK3chr1586213061chr1588576276918GLDSPVAVICTGGATTGGACAGTCCCGTGGCTGTCA

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
AKAP13-NTRK3chr1586213061chr15885762761126DSPVAVISGEEDSASTGGACAGTCCCGTGGCTGTCATCAGTGGTGAGGAGGACTCAGCCA

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Information of the samples that have these potential fusion neoantigens of AKAP13-NTRK3

check button These samples were reported as having these fusion breakpoints. For individual breakpoints, we checked the open reading frames considering multiple gene isoforms and chose the in-frame fusion genes only. Then, we made fusion protein sequences and predicted the fusion neoantigens. These fusion-positive samples may have these potential fusion neoantigens.
Cancer typeFusion geneHchrHbpHenstTchrTbpTenstSample
LGGAKAP13-NTRK3chr1586213061ENST00000361243chr1588576276ENST00000317501TCGA-DB-5277-01A

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Potential target of CAR-T therapy development for AKAP13-NTRK3

check button Predicted 3D structure. We used RoseTTAFold.

check buttonRetention analysis result of each fusion partner protein across 39 protein features of UniProt such as six molecule processing features, 13 region features, four site features, six amino acid modification features, two natural variation features, five experimental info features, and 3 secondary structure features. Here, to provide the retention of the transmembrane domain, we only show the protein feature retention information of those transmembrane features


* Minus value of BPloci means that the break point is located before the CDS.
- In-frame and retained 'Transmembrane'.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note

check button Subcellular localization prediction of the transmembrane domain retained fusion proteins
* We used DeepLoc 1.0. The order of the X-axis of the barplot is as follows: Entry_ID, Localization, Type, Nucleus, Cytoplasm, Extracellular, Mitochondrion, Cell_membrane, Endoplasmic_reticulum, Plastid, Golgi.apparatus, Lysosome.Vacuole, Peroxisome. Y-axis is the output score of DeepLoc. Clicking the image will open a new tab with a large image.
HgeneHchrHbpHenstTgeneTchrTbpTenstDeepLoc result

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Related Drugs to AKAP13-NTRK3

check button Drugs used for this fusion-positive patient.
(Manual curation of PubMed, 04-30-2022 + MyCancerGenome)
HgeneTgeneDrugSourcePMID

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Related Diseases to AKAP13-NTRK3

check button Diseases that have this fusion gene.
(Manual curation of PubMed, 04-30-2022 + MyCancerGenome)
HgeneTgeneDiseaseSourcePMID

check button Diseases associated with fusion partners.
(DisGeNet 4.0)
PartnerGeneDisease IDDisease name# pubmedsSource
TgeneNTRK3C0036341Schizophrenia3PSYGENET
TgeneNTRK3C0041696Unipolar Depression2PSYGENET
TgeneNTRK3C1269683Major Depressive Disorder2PSYGENET
TgeneNTRK3C1332965Congenital Mesoblastic Nephroma2ORPHANET
TgeneNTRK3C0014175Endometriosis1CTD_human
TgeneNTRK3C0017638Glioma1CTD_human
TgeneNTRK3C0019569Hirschsprung Disease1GENOMICS_ENGLAND
TgeneNTRK3C0023467Leukemia, Myelocytic, Acute1CTD_human
TgeneNTRK3C0026998Acute Myeloid Leukemia, M11CTD_human
TgeneNTRK3C0038220Status Epilepticus1CTD_human
TgeneNTRK3C0238463Papillary thyroid carcinoma1ORPHANET
TgeneNTRK3C0259783mixed gliomas1CTD_human
TgeneNTRK3C0269102Endometrioma1CTD_human
TgeneNTRK3C0270823Petit mal status1CTD_human
TgeneNTRK3C0311335Grand Mal Status Epilepticus1CTD_human
TgeneNTRK3C0393734Complex Partial Status Epilepticus1CTD_human
TgeneNTRK3C0525045Mood Disorders1PSYGENET
TgeneNTRK3C0555198Malignant Glioma1CTD_human
TgeneNTRK3C0751522Status Epilepticus, Subclinical1CTD_human
TgeneNTRK3C0751523Non-Convulsive Status Epilepticus1CTD_human
TgeneNTRK3C0751524Simple Partial Status Epilepticus1CTD_human
TgeneNTRK3C1879321Acute Myeloid Leukemia (AML-M2)1CTD_human